Project Summary/Abstract: Depression (target disease of this proposal) affects 34 million Americans including 2 million seniors per year. It is a leading cause of morbidity and mortality in older adults (target population of this proposal). The vascular depression hypothesis (proposed in 1998) remains the most salient theory explaining the onset and perpetuation of depression in older adults. This model is based on the observation that in older adults, white matter hyperintensities (a hallmark of small vessel disease, SVD) are associated with depression onset and perpetuation. Progress in understanding the relationship of small vessel disease with late-life depression has been stymied in part by lack of specificity of white matter hyperintensities which can represent components of edema, gliosis, ischemia, and inflammation. Traditional MR imaging is unable to distinguish between these components, and thus the specific mechanisms that contribute to depression remain unclear. The emergence of ultrahigh field MR imaging allows for greater specificity of the WMH lesions, and other components of small vessel disease. Bringing 7 tesla (T) imaging into mainstream clinical use will be accomplished through 1) having exclusive (over 1.5/3T) application(s) and 2) achieving robust, safe, consistent, and homogenous high-quality images. Through a consortium consisting of experts at University of Pittsburgh combined with collaboration at FDA, University of Minnesota, and Quality Electrodynamics Inc., our goal is to enhance our understanding of the neuropathophysiology, treatment, and management of depression in older adults. We will achieve this goal through the development of robust radiofrequency methodology, as well as pulse sequences that produce 7T images with the aforementioned necessary attributes. This will be paired with complementary 3T MRI at baseline. We will use our recently developed (as well as a proposed) custom designed 7T radiofrequency coil system and pulse sequences that are already being used in disease/patient studies. Based on our preliminary results, the proposed RF solution will provide unprecedented homogeneity and consistency among different subjects/patients, and therefore excellent signal to noise ratio and contrast to noise ratio for detection of components of small vessel disease. The study will examine two cohorts 1) a group of 30 older adults recruited through the Alzheimer's Disease Research Center (ADRC) for developing an MRI to histopathology statistical model of SVD and 2) 60 older adults with late-life depression who will undergo scanning at baseline and after 2 years. The longitudinal 7T MRI and SVD model will be used to help characterize the small vessel changes associated with depression in older adults. In summary, this study develops an emerging and timely technology (high-performance ultrahigh field MRI) to study a critical pathophysiological process (cerebral small vessel disease) in a clinically relevant population (Late-Life Depression). This project will further advance all of these three domains.